AJP - Endocrinology and Metabolism, Vol 255, Issue 2 E173-E179, Copyright © 1988 by American Physiological Society
Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus
A. I. Salhanick and J. M. Amatruda
Department of Medicine, University of Rochester Medical Center, New York 14642.
Adipocytes treated with neuraminidase show markedly reduced responsiveness
to insulin without any alteration in insulin binding. In addition, several
studies have separately demonstrated both insulin resistance and decreases
in membrane sialic acid content and associated biosynthetic enzymes in
diabetes mellitus. In the present study, we investigated the role that
sialic acid residues may play in insulin action and in the hepatic insulin
resistance associated with nonketotic diabetes. Primary cultures of
hepatocytes from normal rats treated with neuraminidase demonstrated a
dose-dependent decrease in insulin-stimulated lipogenesis. At a
concentration of neuraminidase that decreases insulin action by 50%, 23% of
total cellular sialic acid content was released. Neuraminidase-releasable
sialic acid was significantly decreased in hepatocytes from diabetic rats
and this was associated with significant insulin resistance. Treatment of
hepatocytes from diabetic rats with cytidine
5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin
responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA
was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA
effect was catalyzed by a cell surface sialyltransferase. CMP reduced
neuraminidase-releasable [14C]sialic acid incorporation into hepatocytes by
43%. The data demonstrate a role for cell surface sialic acid residues in
hepatic insulin action and support a role for decreased cell surface sialic
acid residues in the insulin resistance of diabetes mellitus.
